Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success.

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